Observational studies have linked IgG N-glycosylation to rheumatoid arthritis (RA), but the causal relationship between the 2 illnesses has yet to be established. To investigate the possible causal correlations of IgG N-glycosylation with RA, standard and multivariable 2-sample Mendelian randomization (MR) analyses incorporating a summary genome-wide association analysis for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were undertaken. The standard MR analysis based on the inverse-variance weighted technique revealed a significant correlation of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4=0.906, 95% CI=0.857–0.958, P=5.246×10−4) after correcting for multiple testing (P<2×10−3). In addition, multivariable MR analysis revealed 7 significant relationships of genetically instrumented IgG N-glycans with RA (P< 2×10−3). Sensitivity tests utilizing MR Lasso, MR weighted median, MR Egger regression, and leave-one-out analysis with different instruments yielded similar results (all P values<0.05). Pleiotropy bias was infrequent (all P values>0.05). Finally, the MR analysis, which included genome-wide association studies and IgG N-glycan-QTL data, suggested that IgG N-glycans might be causally linked to RA. The outcomes offer light on IgG N-role glycosylations in the progression of RA. Future research was needed to confirm the findings and investigate the physiological mechanisms underlying the genesis of RA.